In bacteria, glutamine synthetase is "marked" for subsequent proteolytic degradation by a covalent modification. This modification involves oxidation of a specific histidine residue. A cyanogen bromide fragment containing the altered histidine has been isolated. The peptide has only a few residues (less than 10) and is very hydrophilic in behavior. Glutamine synthetase which has been oxidatively modified in vitro reacts with 2,4 dinitrophenylhydrazine to form a hydrazone. The molar absorptivity is proportional to the extent of oxidative modification. When purified preparations of glutamine synthetase were isolated by our usual method, they also formed phenylhydrazones. The extent of reaction was inversely proportional to their specific activity. Thus, the oxidative modification probably occurs in vivo and accounts for variability in specific activity of purified enzyme preparations. Oxidative modification may provide another mechanism for regulation of metabolic activity by covalent modification of proteins. In particular, the modification appears to mark glutamine synthetase for proteolytic degradation.